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. 2021 Jul 20;37(11):1625–1636. doi: 10.1007/s12264-021-00751-3

Table 1.

Summary of recent approaches to glia-to-neuron conversion in vitro and in vivo.

Glial source Region Targeted TFs Small molecules/micro RNA/Others Neuronal type Conversion efficiency Ref.
Mouse Astrocyte in vitro (cultured cell) Forskolin, ISX9, CHIR99021, I-BET151 Glut+/GABA+ High [49]
Cortex NeuroD1 Glut+ neuron High [37]
Cortex Ngn2 GEND1 GABA+/TH+ cell High [50]
Cerebral cortex Ngn2 Glut+ neuron High [23, 24, 56]
Cerebral cortex Pax6 Undefined ? [21, 23]
Cerebral cortex NeuroD4+ Insm1 Glut+ neuron Low [56]
Cerebral cortex Dlx2 GABA+ neuron Low [24]
Cerebral cortex Ascl1+ Dlx2 Interneurons High
Cerebral cortex Ascl1 Undefined Low [23, 56]
Ascl1+Lmx1b+Nurr1 Dopaminergic neuron Low [25]
Midbrain Ascl1+Phox2b+AP−2α+Gata3+Hand2+Nurr1+Phox2a Noradrenergic neuron High [82]
Dorsal midbrain Ascl1 Glut+/GABA+ High [42]
in vivo Midbrain Ascl1 Glut+/GABA+ High [42]
Striatum Ascl1+Lmx1a+ Nurr1 Glut+ (16%)/GABA+ (68%) ? [39]
Striatum Ascl1+Lmx1a+NeuroD1 miR218 Dopaminergic neuron Low [41]
Striatum Ascl1+Brn2a+Myt1l Un-defined Low [27]
Striatum Forskolin+ CHIR99021+ IBET151+ISX9+Y-27632 GABA+ (87.1%) low [49]
Striatum NeuroD1 + Dlx2 GABA+ neuron High [38]
Striatum Ngn2 FGF2+EGF GABA+ neuron Low [33]
Striatum Sox2 DCX+ cell ? [28, 29]
Spinal cord Sox2 VPA GABA+ neuron Low [30]
Substantia nigra PTB/sh RNA Dopaminergic (30 %)/Others high [45]
Cortex Forskolin+ CHIR99021+ IBET151+ISX9+Y−27632 Glut+ (72.8%) Low [49]
Cortex NeuroD1 Undefined High [37]
Cortex Ngn2 FGF2+EGF Glut+ neuron Low [33]
Cerebral cortex Ngn2+Nurr1 Pyramidal neuron High [35]
Cerebral cortex Ascl1+Nurr1 Undefined High
Motor cortex NeuroD1 Pyramidal neuron(90%)/GABA+ (10%) High [36]
NG 2 cell in vitro Cortex NeuroD1 Glut+ (90%)/GABA+ (10%) neuron High [37]
in vivo Cortex NeuroD1 Undefined High [37]
Spinal cord Sox2 Glut+/GABA+ High [32]
Cerebral cortex Sox2 DCX+ cell Low [31]
Cerebral cortex Ascl1+ Lmx1a + Nurr1 Glut+ (16%)/GABA+ (68%) neuron High [39, 40]
Striatum siRNAs 3/4 GABA+ neuron High [46]
Microglia in vitro NeuroD1 Glut+ (74.2%) / GABA+ (25.7%) Low [56]
in vivo Striatum NeuroD1 Striatal neuron High [56]
Müller glia in vitro Ascl1 Bipolar cell Low [55]
Ascl1 Multipolar/uni/bipolar cells High [80]
Ngn2 Unipolar/bipolar cell High
in vivo Injured retina Ascl1 Bipolar/amacrine cell ? [43]
Injured retina Ascl1 TSA Bipolar cell ? [61]
Human Astrocytes in vitro Cortex LDN193189+ SB431542+ TTNPB+Tzv+ CHIR99021+ VPA+DAPT+ SAG+Purmo Glut+ (88%)/GABA+ (8.2%) neuron High [14]
Cortex SB431542+ LDN193189+ CHIR9902+ DAPT Glut+ (78%)/GABA+ (2%)/Dopaminergic (1%) High [48]
Cortex NeuroD1 Glut+ neuron High [37]
NeuroD1+Ascl1+ Lmx1a miR218 Dopaminergic neuron Low [41]
NG2 cell in vitro Sox2+Dlx5+Lhx6+ Ascl1+Foxg1 sh REST GABA+ neuron high [84]
Ascl1+Lmx1a+Nurr1 sh REST Dopaminergic neuron ? [85]

TFs transcription factors, GABAergic (GABA+) or glutamatergic (Glut+) neurons; high efficiency: reprogramming ratio >35%.